Diaglinide® (Diaglinid®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
Read on
Active substanceRepaglinideRepaglinide
Similar drugsTo uncover
  • Diaglinide®
    pills inwards 
    AKRIKHIN HFK, JSC     Russia
  • Iglynide
    pills inwards 
    Pharmasintez-Tyumen, Open Company     Russia
  • Novonorm®
    pills inwards 
    Novo Nordisk A / S     Denmark
    • Dosage form: & nbspPills.

    Composition:One tablet contains:
    active substance:     repaglinide in terms of 100% substance - 0.5 mg, 1 mg and 2 mg;
    Excipients: poloxamer 3 mg, 3 mg or 3 mg; meglumine 10 mg, 10 mg or 13 mg; lactose monohydrate 47.8 mg, 47.5 mg or 61.7 mg; cellulose microcrystalline 33.7 mg, 33.45 mg or 45 mg; polucrilin potassium 4 mg, 4 mg or 4 mg; silicon dioxide colloid 0.5 mg, 0.5 mg or 0.7 mg; magnesium stearate 0.5 mg, 0.5 mg or 0.6 mg; ferric iron oxide yellow (for tablets with a dosage of 1 mg) 0.05 mg respectively.

    Description:Tablets are flat-cylindrical, with a bevel. Tablets with a dosage of 0.5 mg and 2 mg of white with a creamy or yellowish hue of color. Tablets with a dosage of 1 mg from light yellow to yellow with interspersed.

    Pharmacotherapeutic group:Hypoglycemic agent for oral administration.
    ATX: & nbsp

    A.10.B.X   Other hypoglycemic drugs

    A.10.B.X.02   Repaglinide

    Pharmacodynamics:Oral hypoglycemic agent, stimulates the release of insulin from the functioning beta cells of the pancreas. It blocks ATP-dependent channels in beta-cell membranes by means of target proteins,which leads to depolarization of beta-cells and the opening of calcium channels. Increased influx of calcium ions induces insulin secretion. In patients with type 2 diabetes, an insulinotropic response to food intake is observed within 30 minutes after ingestion. This ensures a decrease in the concentration of glucose in the blood during the entire period of ingestion. At the same time, the concentration of repaglinide in plasma rapidly decreases, and 4 hours after taking the drug in plasma of patients with type 2 diabetes, low concentrations of repaglinide are found. When applying repaglinide in the dose range from 0.5 to 4 mg, a dose-dependent decrease in glucose concentration is noted.

    Pharmacokinetics:When ingestion, the absorption of repaglinide from the gastrointestinal tract is high. The time to reach the maximum concentration is 1 hour. The average bioavailability of repaglinide is 63% (the coefficient of variability is 11%). Since titration of repaglinide dose is carried out depending on the response to therapy, interindividual variability does not affect the effectiveness of therapy.
    The volume of distribution is 30 liters. The connection with plasma proteins is 98%. It is completely metabolized in the liver under the influence of CYP3A4 to inactive metabolites. It is excreted mainly with bile, kidneys - 8% in the form of metabolites, through the intestine - 1%.Half-life is 1 hour.
    Liver failure
    The use of repaglinide in normal doses in patients with impaired liver function can lead to a higher concentration of repaglinide and its metabolites than patients with normal liver function. In this regard, the use of repaglinide is contraindicated in patients with severe impairment of liver function, and in patients with impaired hepatic and mild liver function repaglinide should be used with caution. Also, the intervals between dose adjustments should be increased in order to more accurately assess the response to therapy.
    Renal insufficiency
    The area under the concentration-time curve (AUC) and the maximum concentration of repaglinide in plasma (C) are the same in patients with normal renal function and in patients with impaired renal function of mild or moderate severity. In patients with severe renal dysfunction, there was an increase in AUC and C, but there was a weak correlation between repaglinide concentration and creatinine clearance. It seems that patients with impaired renal function do not need to adjust the initial dose.However, a subsequent increase in dose in patients with type 2 diabetes combined with severe renal dysfunction requiring hemodialysis should be carried out with caution.

    Indications:Diabetes mellitus type 2 (with diet inefficiency, weight loss and exercise) in monotherapy or in combination with metformin or thiazolidinediones in cases where it is not possible to achieve satisfactory control of glycemia with monotherapy with repaglinide or metformin or thiazolidinediones.

    Contraindications:- known hypersensitivity to repaglinide or to any of the components of the drug;
    - Type 1 diabetes mellitus;
    - diabetic ketoacidosis; diabetic precoma and coma;
    - infectious diseases, large surgical interventions and other conditions requiring insulin therapy;
    severe liver dysfunction;
    - simultaneous administration of gemfibrozil (see Interaction with other drugs);
    - Lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
    - pregnancy and the period of breastfeeding;
    - age to 18 years.
    Clinical studies in patients under the age of 18 years and older than 75 years were not conducted.

    Carefully:(the need for more careful observation) should be used for violations of liver function of mild and moderate degree, febrile syndrome, chronic renal failure, alcoholism, general severe condition, malnutrition.

    Pregnancy and lactation:Studies on the use of repaglinide in pregnant women and nursing mothers have not been conducted. Therefore, the safety of repaglinide in pregnant women has not been studied. If you need to use the drug during breastfeeding, breastfeeding should be discontinued.

    Dosing and Administration:Diaglinide is prescribed as an adjunct to diet and exercise in order to reduce the concentration of glucose in the blood, its administration should be timed to meals.
    The drug is taken orally in front of the main meals, usually 15 minutes before the start of the meal, but can also be taken in the range of 30 minutes before meals until the immediate moment of ingestion.
    The dose of the drug is selected individually for each patient, depending on the concentration of glucose in the blood.
    The initial dose is 0.5 mg / day (if the patient took another oral hypoglycemic drug - 1 mg). Correction of the dose is carried out once a week or once in 2 weeks (while focusing on the concentration of glucose in the blood as an indicator of response to therapy). The average daily dose is 4 mg 3 times a day; maximum -16 mg / day.
    Transfer of patients with therapy with other oral hypoglycemic drugs on repaglinide therapy can be carried out immediately. At the same time, there was no exact correlation between the dose of repaglinide and the dose of other hypoglycemic drugs. The recommended maximum initial dose of repaglinide when transferred from other hypoglycemic drugs is 1 mg before the main meal.
    Combination Therapy
    Repaglinide may be administered in combination with metformin or thiazolidinediones in the case of inadequate glucose control in monotherapy with metformin, thiazolidinediones or repaglinide. In this case, the same initial dose of repaglinide is used, as in monotherapy. Then adjust the dose of each drug, depending on the reached concentration of glucose in the blood.
    Special groups of patients (see section "Special instructions").
    It is not recommended to appoint repaglinide persons under the age of 18 due to the lack of sufficient data on its safety and efficacy in this group of patients.

    Side effects:

    The most common side effect is hypoglycemia, the frequency of which depends, as with any kind of diabetes therapy, on individual factors such as eating habits, the dose of the drug, physical activity and stress.

    Below are the side effects observed with repaglinide and other oral hypoglycemic agents. All side effects are divided into groups according to the frequency of development, defined as: often (>1/100 to <1/10); infrequently (>1/1000 to <1/100); rarely (>1/10000 to <1/1000); very rarely (<1/10000) and it is not known (it is impossible to estimate on the basis of available data).

    Immune system disorders
    Very rarely: generalized hypersensitivity reactions or immunological reactions, such as vasculitis, can be detected.
    Unknown: hypersensitivity reactions, such as pruritus, rash, urticaria.
    Metabolic disorders
    Often: hypoglycemia.
    Unknown: hypoglycemic coma, hypoglycemia with loss of consciousness.
    As with other hypoglycemic agents, hypoglycemia may develop with repaglinide. In most cases, these reactions are mild and can be eliminated by taking carbohydrates. In severe reactions, medical attention may be required, in particular, intravenous dextrose (glucose). The risk of developing hypoglycemia may increase with the interaction of repaglinide with other drugs (see section "Interactions with other drugs").
    Disturbances on the part of the organ of sight
    Very rarely: visual disturbances.
    Changes in the concentration of glucose in the blood can lead to visual disturbances, especially at the initial stage of therapy with hypoglycemic drugs. However, usually these changes are transient.
    Disorders from the cardiovascular system
    Rarely: cardiovascular diseases.
    The risk of cardiovascular disease is increased in type 2 diabetes mellitus. There was an increased risk of acute coronary syndrome in patients who received repaglinide, compared with patients receiving the sulfonylurea derivative, but not compared to patients receiving metformin or acarbose. However, a causal relationship is not established.
    Disorders from the digestive system
    Often: abdominal pain, diarrhea.
    Very rarely: vomiting, constipation.
    Unknown: nausea.
    Disturbances from the liver and bile ducts
    Very rarely: violations of the liver.
    In very rare cases, serious violations of liver function have been reported, however, a causal relationship with repaglinide has not been established.
    Very rarely: increased activity of "liver" enzymes.

    Overdose:Overdose may develop hypoglycemia. Symptoms: hunger, increased sweating, palpitation, tremors, anxiety, headache, insomnia, irritability, depression, speech and vision impairment.
    When using repaglinide in patients with type 2 diabetes in a weekly increasing dose of 4 to 20 mg 4 times a day (with each meal) for 6 weeks, there was a relative overdose showing an excessive decrease in glucose concentration with the development of symptoms of hypoglycemia.
    In case of symptoms of hypoglycemia, appropriate measures should be taken to increase the concentration of glucose in the blood (ingest dextrose or foods rich in carbohydrates). In severe hypoglycemia (loss of consciousness, coma) intravenously injected with dextrose. After the restoration of consciousness - the reception of digestible carbohydrates (to avoid the re-development of hypoglycemia).

    Interaction:It is necessary to take into account the possible interaction of repaglinide with drugs that affect glucose metabolism.
    Metabolism, and thus clearance of repaglinide, can change under the influence of drugs that have an effect by suppressing or activating enzymes from the cytochrome P-450 group. Particular care should be taken with the simultaneous administration of repaglinide inhibitors CYP2C8 and CYP3A4. Inhibitors of the anatransporting protein OATPlBl (eg, ciclosporin) can also increase the concentration of repaglinide in plasma.
    The following drugs can enhance and / or prolong the hypoglycemic effect of repaglinide:
    Gemfibrozil, trimethoprim, rifampicin, clarithromycin, ketoconazole, itraconazole, ciclosporin, other hypoglycemic drugs, monoamine oxidase inhibitors, nonselective beta adrenoblockers, angiotensin converting enzyme inhibitors, salicylates, non-steroidal anti-inflammatory drugs (NSAIDs), octreotide, ethanol and anabolic steroids.
    Beta-blockers can mask symptoms of hypoglycemia.
    Simultaneous administration of cimetidine, nifedipine or simvastatin (being substrates CYP3A4) with repaglinide does not significantly affect the pharmacokinetic parameters of repaglinide.
    Repaglinide does not clinically significantly affect the pharmacokinetic properties of digoxin, theophylline, or warfarin when used in healthy volunteers. Thus, there is no need to adjust the dose of these drugs when combined with repaglinide.
    The following drugs can weaken the hypoglycemic effect of repaglinide:
    Oral contraceptives, rifampicin, barbiturates, carbamazepine, thiazides, glucocorticosteroids, danazol, thyroid hormones and sympathomimetics.
    Joint application oral contraceptives (ethinyl estradiol / levonorgestrel) does not lead to a clinically significant change in the overall bioavailability of repaglinide, although the maximum concentration of repaglinide is reached earlier. Repaglinide clinically significant does not affect the bioavailability of levonorgestrel, but its effect on the bioavailability of ethinylestradiol can not be ruled out.
    In connection with this, during the appointment or cancellation of the above drugs, patients already receiving repaglinide, should be carefully monitored for the timely detection of a violation of glycemic control.

    Special instructions:Repaglinide is shown at unsatisfactory control of a glycemia and preservation of symptoms of a diabetes mellitis on a background of dietotherapy and physical exercises.
    Because the repaglinide is a preparation that stimulates the secretion of insulin, it can cause hypoglycemia. With combined therapy, the risk of hypoglycemia increases.
    Large surgical interventions and trauma, extensive burns, infectious diseases with febrile syndrome may require the abolition of oral hypoglycemic drugs and the administration of insulin.
    It is necessary to regularly monitor the concentration of glucose in the blood on an empty stomach and after eating. The patient should be warned about the increased risk of hypoglycemia in cases of alcohol intake, NSAIDs, and fasting.
    Dose correction is necessary in case of physical and emotional overstrain, changes in diet.
    In patients with malnutrition, as well as patients receiving malnutrition, care should be taken when choosing an initial and maintenance dose, and titration, to avoid hypoglycemia.
    Special patient groups
    Renal insufficiency
    Dose selection in patients with type 2 diabetes combined with severe renal dysfunction should be done with caution.
    Liver failure
    The administration of conventional doses of repaglinide in patients with impaired liver function can lead to a higher concentration of repaglinide and its metabolites than patients with normal liver function. In this regard, the appointment of repaglinide is contraindicated in patients with severe impairment of liver function (See section "Contraindications"), and in patients with mild to moderate liver dysfunction repaglinide should be used with caution.Also, the intervals between dose adjustments should be increased in order to more accurately assess the response to therapy.

    Effect on the ability to drive transp. cf. and fur:The ability of patients to concentrate and respond to the reaction may be impaired during hypoglycemia and hyperglycemia, which can be dangerous in situations where this ability is especially needed (for example, when driving vehicles or working with machines and mechanisms). Patients should be advised to take measures to prevent the development of hypoglycemia and hyperglycemia in the management of vehicles and work with mechanisms. This is especially important for patients with a lack or decrease in the severity of symptoms-precursors of developing hypoglycemia or suffering from frequent episodes of hypoglycemia. In these cases, you should consider the feasibility of doing such work.

    Form release / dosage:Tablets 0.5 mg, 1 mg and 2 mg.

    Packaging:For 10 tablets in a planar cell package. 3 or 6 contour squares with instructions for use in a pack of cardboard.

    Storage conditions:

    In dry, dark place at a temperature of no higher than 25 ° C.
    Keep out of the reach of children.

    Shelf life:2 years. Do not use after expiry date.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-001261
    Date of registration:22.11.2011
    The owner of the registration certificate:AKRIKHIN HFK, JSC AKRIKHIN HFK, JSC Russia
    Manufacturer: & nbsp
    Representation: & nbspAKRIKHIN OJSC AKRIKHIN OJSC Russia
    Information update date: & nbsp08.08.2015
    Illustrated instructions
      Instructions
      Up